rs2305743

chr19-18082381-G-Achr19-18082381-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005535.3(IL12RB1):c.125-117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 707,256 control chromosomes in the GnomAD database, including 13,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2772 hom., cov: 31)
  • Exomes 𝑓: 0.19 (10894 hom.)
• Consequence: IL12RB1 NM_005535.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.37

Genes affected

IL12RB1 (HGNC:5971): (interleukin 12 receptor subunit beta 1) The protein encoded by this gene is a type I transmembrane protein that belongs to the hemopoietin receptor superfamily. This protein binds to interleukine 12 (IL12) with a low affinity, and is thought to be a part of IL12 receptor complex. This protein forms a disulfide-linked oligomer, which is required for its IL12 binding activity. The coexpression of this and IL12RB2 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. Mutations in this gene impair the development of interleukin-17-producing T lymphocytes and result in increased susceptibility to mycobacterial and Salmonella infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-18082381-G-A is Benign according to our data. Variant chr19-18082381-G-A is described in ClinVar as [Benign]. Clinvar id is 2688457.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL12RB1	NM_005535.3	c.125-117C>T		intron_variant		ENST00000593993.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL12RB1	ENST00000593993.7	c.125-117C>T		intron_variant		1	NM_005535.3	P1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28405 AN: 151768 Hom.: 2768 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.193 AC: 107155 AN: 555370 Hom.: 10894 AF XY: 0.190 AC XY: 56927 AN XY: 299526

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.192

GnomAD4 genome AF: 0.187 AC: 28429 AN: 151886 Hom.: 2772 Cov.: 31 AF XY: 0.186 AC XY: 13815 AN XY: 74228

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.181

Alfa AF: 0.201 Hom.: 6445

Bravo AF: 0.178

Asia WGS AF: 0.130 AC: 456 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 31% of patients studied by a panel of primary immunodeficiencies. Number of patients: 27. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.84
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2305743; hg19: chr19-18193191; COSMIC: COSV59097571; COSMIC: COSV59097571;